Infection with herpes simplex type 1 (HSV-1) induces expression of receptors for C3b on mammalian cells previously devoid of such receptors. We have shown that the isolated glycoprotein responsible for this activity (gC) is a potent modulator of complement-mediated cytolysis in-vitro, acting by at least two mechanisms. We have demonstrated that herpes simplex type 2 (HSV- 2) also induces expression of a C3b binding protein which corresponds to HSV-I gC, but has different regulatory properties vis-a-vis the complement cascade. Binding requirements relating to glycosylation have been explored in a purified protein system for both gC-I and gC-2. Transient expression systems in mammalian cells and a stably tranfected murine cell line which expresses gC- I under the control of an inducible promoter have been developed in the laboratories of Drs. Friedman and Cohen, and these systems are in use to study the binding site for C3b and also to explore the biologic consequences of the expression of gC vis-a-vis complement dependent host defense processes. Ongoing studies of parainfluenza virus type 3 have shown that certain IgM monoclonal antibodies to the hemagglutinin- neuraminidase protein can produce neutralization in the presence of an active complement cascade. This activity is dependent in toto on viral lysis. The antibodies do not function by initiating complement activation. The virus itself is a spontaneous activator of the classical pathway, an event which proceeds through specific binding of C1 from non-immune sera or in the purified state. Active monoclonals induce no overall enhancement of complement fragment uptake through C3, although late component binding is somewhat enhanced. This latter finding does not clearly distinguish monoclonals which produce synergistic complement- dependent neutralization from those that do not, however. Current studies are directed ar elucidating how active monoclonals enhance the efficacy of the complement late components and one potential biologic implications of the C1 binding interaction.